How can minute quantities of chemicals such as sarin overwhelm the nervous system of an adult human so quickly?

Michael Allswede is an emergency physician and medical toxicologist at the University of Pittsburgh and a senior research fellow at the University's Center for Biosecurity. He is the author of the RaPiD-T Program (Recognition, Protection, Decontamination, and Treatment) and has trained first responders in chemical weapon management since 1997.

The four factors that determine how a chemical will affect the human body are absorption, distribution, elimination and potency. Absorption refers to the ability of the chemical to enter the body rapidly. In newsworthy events involving carfentanyl and sarin, victims were dosed by way of vapor exposure. In these instances absorption occurred through the lungs, which have a huge surface area and are very efficient at taking up chemicals. Nicotine blood levels in a smoker, for example, rise almost immediately after inhalation. In contrast, absorption through the skin or clothing requires a greater dose and more time and may not occur at all if the chemical cannot penetrate the skin, as in the case of carfentanyl.

Distribution refers to where in the body the chemical goes to exert its effects. To infiltrate the nervous system, a chemical must possess a certain degree of lipid (fat) solubility. Carfentanyl and sarin both rapidly penetrate the lipid brain barrier. Elimination describes how fast the body can rid itself of the chemical and recover from its effects.

A chemicals potency is its ability to exert effects at its site of action. The most potent chemicals act on physiologic receptors within the body and the degree of binding of the chemical to the receptor determines its potency. Carfentanyl binds to the human opiate receptor thousands of times stronger than morphine or heroin does. Indeed, the fentanyl family of synthetic opiates was developed as rapid-acting, high-potency anesthesia medication: carfentanyl overdose causes death by rapidly sedating the individual and halting breathing.

Sarin's potency stems from the inhibition of a very important enzyme in the body called acetyl cholinesterase. This enzyme acts as an off switch to the part of the nervous system that controls voluntary movements such as breathing, as well as bronchial constriction secretion, urinary and bowel continence, and other involuntary functions. When acetyl cholinesterase is inhibited, the nervous system is over-stimulated and the body is paralyzed, breathing stops and the lungs no longer function. Because there is only a small amount of acetyl cholinesterase in the body, very little sarin is needed to induce this effect.

The combination of rapid absorption through the lungs, rapid distribution to the sites of activity, and high potency produces the swiftly lethal toxic effect observed in both carfentanyl and sarin vapor exposure. Vapor toxicity is described in terms of the lethal concentration-time product, or LCt50. LCt50 refers to the death of 50 percent of subjects exposed to a certain concentration over a certain time. For example, the LCt50 for isopropyl methylhosphonofluridate, or sarin, is 100 milligrams per minute per cubic meter. (100 milligrams of pure sarin would look like a small droplet.) That means that if a person is breathing air with a concentration of 100 milligrams per cubic meter, she will live about one minute before she has a 50 percent chance of dying. Smaller people or those breathing faster will be the most susceptible in the event of exposure.

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